(a) Field of the Invention
The present invention relates to an immune-enhancing peptide, and more specifically to an immune-enhancing peptide that can induce superoxide generation in human monocytes.
(b) Description of the Related Art
Reactive oxygen species (ROS) such as superoxide, hydrogen peroxide, and hydroxyl radicals are generated by phagocytic cells upon activation by invading microorganisms or inflammatory debris (1, 2). The production of these ROS enables the phagocytes such as monocytes to play a critical role in human immune responses. The activation of the ROS generation system, which is one of the earliest steps in the host defense against invading microorganisms, is tightly regulated in the immune systems (1-3). To perform their proper roles, monocytes in the resting state have to be activated, and this is a very critical aspect of the host defense mechanism.
Monocyte activation can be induced by various extracellular stimuli such as bacterial endotoxins (lipopolysaccharides), immunoglobulins, and several chemoattractants (4-7). Among these extracellular stimuli, chemoattractants including several chemokines that regulate the activities of monocytes have been receiving attention for a long time. Many chemoattractants stimulate leukocytes via the activation of pertussis toxin (PTX)-sensitive G-protein-coupled receptors (1). Upon binding to its corresponding cell surface receptor, a chemoattractant induces intracellular Ca2+ mobilization, cytoskeletal rearrangements, exocytosis, histamine release, receptor induction, adhesion, the production of bioactive lipids, and the activation of the respiratory burst system via NADPH oxidase activation (1, 8, 9). With this important role of chemoattractants for monocyte functions in mind, the identification of new chemoattractants and the characterization of their mechanisms of action are very much needed.
Recently, several studies have reported the use of combinatorial peptide libraries to identify sequences involved in various biological responses. Houghten et al. developed a method for a positional scanning synthetic peptide combinatorial library (PS-SPCL) that is an easy and powerful tool for identifying peptide sequences in certain biological reactions (10). This method has been adopted for various purposes including the identification of human immunodeficiency virus protease inhibitors, interleukin-8-specific antagonists, inhibitors for nuclear factors of activated T cells, and ligands for opioid receptors (11-14). Also, the present inventors have already identified one bioactive hexapeptide that stimulates phosphoinositide hydrolysis, by screening hexapeptide combinatorial libraries (15). However, the research thus far has been very limited, and therefore there are continuing demands for identifying novel agents.